pHPT Patients Research Articles

Beck Depression Inventory-II Response Following Parathyroidectomy for Primary Hyperparathyroidism: A Systematic Review and Meta-Analyses.

There is currently a lack of consensus regarding neuropsychiatric symptoms as an indication for parathyroidectomy in primary hyperparathyroidism (pHPT). The purpose of this study is to perform a systematic review and meta-analyses of pre- and postoperative Beck Depression Inventory-II (BDI-II) scores in patients with pHPT undergoing parathyroidectomy. A search of the literature was performed using Embase, PubMed, Web of Science, PsycINFO, and OvidAll EBM Reviews. Studies were included if they evaluated BDI-II scores in pHPT patients before and after parathyroidectomy. The literature search returned 1554 studies, of which nine articles met criteria for inclusion. Baseline BDI-II scores were significantly higher in pHPT patients compared to control patients. pHPT patients experienced a statistically significant decrease in BDI-II scores at ≤ 1 and 6 months postoperatively. Based on the results of this study, a BDI-II score ≥ 14 could potentially advocate for parathyroidectomy in patients with pHPT.

Diagnostic Accuracy of Four-Dimensional Computed Tomography in Preoperative Localization of Primary Hyperparathyroidism After Negative or Inconclusive Sestamibi: A Systematic Review and Meta-analysis

Objective The aim of the study is to assess the diagnostic accuracy of 4-dimensional computed tomography (4D-CT) scans for patients with primary hyperparathyroidism (pHPT) after negative or inconclusive Technetium-99m sestamibi single-photon emission computed tomography scan. Methods A literature search of several databases was conducted from inception to August 2023. Eligible studies reported adult patients (>18 years old) who underwent 4D-CT after negative or inconclusive sestamibi results. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023446285). Results From 208 initial studies screened, 10 met the eligibility criteria, with a total of 335 patients with a diagnosis of pHPT who underwent 4D-CT scans and subsequent surgical exploration. Nine of the studies reported a pooled sensitivity of localization of 71% (0.71; 95% confidence interval [CI]: 0.610, 0.811, I 2 = 72%). The pooled specificity of localization across 5 studies was calculated at 47% (0.47; 95% CI: −0.111, 1.059, I 2 = 99%). Seven of the included studies reported a pooled positive predictive value of 81% (0.81; 95% CI: 0.708, 0.917, I 2 = 70%), and 6 of the studies reported a negative predictive value of 28% (0.28; 95% CI: −0.114, 0.683, I 2 = 98%). Conclusions For pHPT patients with inconclusive sestamibi scans, 4D-CT demonstrates promising results with good diagnostic accuracy for the localization of pHPT. Additional studies evaluating larger groups of patients may provide further support for the use of 4D-CT in this population.

Refining the role of presurgical PET/4D-CT in a large series of patients with primary hyperparathyroidism undergoing [18F]Fluorocholine PET/CT.

4D-CT has garnered attention as complementary imaging for patients with primary hyperparathyroidism (pHPT). Herein we evaluated a diagnostic strategy using [18F]Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT), followed by 4D-CT integrated into PET/4D-CT after negative/inconclusive PET/CT results in a single-center retrospective cohort of 166 pHPT patients who underwent parathyroidectomy after [18F]Fluorocholine PET/4D-CT. PET/CT and 4D-CT images were interpreted by three nuclear medicine physicians and one expert radiologist. Pathological findings were documented, and concordance rates were assessed. PET/CT results were categorized as positive/negative, with positive cases rated on a 3-level certitude scale: low, moderate, high. Inconclusive cases included low/moderate positivity. The added value of PET/4D-CT was assessed for negative/inconclusive cases through joint reading. PET/CT lesion-based analysis showed almost perfect interobserver concordance (Cohen's kappa >.8). Across the cohort, PET/CT had a sensitivity of 83%, specificity of 97%, PPV of 90% and NPV of 94%. For 4D-CT, these values were sensitivity: 53%, specificity: 84%, PPV: 56% and NPV: 82%. PET/CT was significantly more accurate than 4D-CT. Among 44 patients with negative/inconclusive results, PET/CT had sensitivity: 60%, specificity: 91%, PPV: 71% and NPV: 86%. In the same patients, sensitivity and specificity of the sequential diagnostic algorithm increased to 80% and 97%, showing significantly better global accuracy (92% vs. 83%) than standard PET/CT. We support a personalized imaging algorithm for pHPT, placing [18F]Fluorocholine PET/CT at the forefront, followed by 4D-CT integrated into PET/4D-CT in the same imaging session for negative/inconclusive results. When PET/CT results are clearly positive, the additional sensitivity benefit of 4D-CT is minimal.

Association between radius axial low-frequency ultrasound velocity and bone fragility in primary hyperparathyroidism.

Radius quantitative ultrasound measurement, that utilized a portable low-frequency (VLF) axial transmission ultrasound for assessing the properties of radius cortical bone in a non PHPT population revealed a possible role as a screening tool prior to DXA to evaluate fragility fracture. To evaluate this portable ultrasound device as a screening tool of skeletal fragility in PHPT patients. We enrolled 117 postmenopausal women with PHPT. Every subject had a DXA of femur, lumbar spine, non-dominant distal 1/3 radius, TBS measurement, VLF with a portable device and spine x- ray. The mean age of the patients was 68 ± 10 years. The measurement of agreement between radius DXA and VLF was: K = 0.43, p < 0.001. A lower radius US T-score, also adjusted for years since menopause and BMI, was associated with osteoporosis identified with DXA at lumbar and/or femoral neck sites: OR = 1.852 (CI 1.08, 3.18). All fractures were associated with femoral neck T-score: OR = 1.89 (95% CI 1.24, 2.89), as well as with total hip T-score: OR = 1.65 (95% CI 1.09, 2.50), and years since menopause: OR = 1.25 (95% CI 1.02, 1.54).Morphometric vertebral fractures were associated with years since menopause: OR = 1.28 (95% CI 1.02,1.61), femoral neck T-score OR = 1.96 (95% CI 1.227, 3.135), total hip T-score OR = 1.64 (95% CI 1.04, 2.60), TBS OR = 0.779 (95% CI 0.60-0.99), both ultra-distal radius T-score: OR = 1.50 (95% CI 1.05, 2.156), and radius US T-score: OR = 1.67 (95% CI 1.09, 2.56). VLF could be used for screening purposes prior to DXA to evaluate PHPT fracture risk, only in conditions in which DXA measurement cannot be performed.

Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study

To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Reducing disparities in the treatment of hyperparathyroidism

BackgroundHyperparathyroidism is common with African American patients historically experiencing disparate outcomes. With a comprehensive outreach program and systematic treatment plans, we sought to evaluate our institution's ability to reduce disparities in hyperparathyroidism. MethodsWe performed a retrospective review of prospectively collected data at a single medical center for all patients undergoing parathyroidectomy by endocrine surgeons from 2015 to 2021 for primary (PHPT) and tertiary (THPT) hyperparathyroidism. Patient demographics, pre-and post-operative clinical and biochemical data were collected and analyzed by race. ResultsOf the 757 patients included, 675 patients had PHPT with 135 (20 %) African-American (AA) and 528(78 %) female. Of 82 patients with THPT, 44 (53 %) were AA and 34 (32 %) were female. AA patients were younger than Caucasian (CA) patients with a mean age (±SD) of 56 ± 15 vs 60 ± 14 years in PHPT (p < 0.01) and 50 ± 10 vs 55 ± 10 years in THPT (p = 0.02).Median (IQR) preoperative PTH was higher in AA with PHPT 134 (97–190) vs 102 (75–144) pg/mL (p < 0.01) and in AA with THPT 285 (189–544) vs 218 (145–293) (p = 0.01) pg/mL. AA PHPT patients had significantly higher preoperative mean (±SD) calcium levels 10.9 ± 0.8 vs 10.6 ± 0.8 mg/dL(p < 0.001). Biochemical cure rates at 6 months and complication rates were not different between races. ConclusionsAA patients with PHPT and THPT disease experienced similar cure rates to their CA counterparts despite having a more severe biochemical disease. Health care disparities may be ameliorated with treatment by high volume surgeons embedded in a comprehensive health care system.

O-14 A rare case of hypercalcaemia in pregnancy

Abstract Introduction Hypercalcaemia is infrequent during pregnancy, but it is associated with foetal and maternal morbidity and mortality. Although primary hyperparathyroidism (pHPT) accounts for the majority of the cases, other aetiologies such as genetic causes in a young population should be considered. Clinical Case A 27-year-old female was diagnosed with pHPT during her 16th week of gestation after she presented with vomiting and was found to have raised adjusted calcium of 3.22 mmol/L, low phosphate of 0.6 mmol/L and Parathyroid Hormone of 10.6 pmol/L. The patient's hypercalcaemia dated back 2 years, she had a history of three previous miscarriages, and was not on any hypercalcaemia-inducing medications. Unbeknownst to her, her father was also being evaluated for hypercalcaemia. Her thyroid-stimulating hormone was fully suppressed with raised free thyroid hormones and negative TSH receptor antibodies; this was improved with Carbimazole therapy. Plasma and urine Metanephrines were normal, and neck ultrasound did not reveal any parathyroid lesions. She underwent parathyroidectomy three weeks later after a period of intravenous hydration. A 2 cm left superior parathyroid adenoma was excised, and the plasma calcium level promptly normalised. Genetic testing for familial hyperparathyroidism revealed an autosomal dominant heterozygous CDC73 variant, which is associated with Hyperparathyroidism-Jaw Tumour syndrome. The Clinical Genetics team is arranging genetic testing for her first-degree relatives. She delivered a live baby at 38 + 6 weeks of gestation via emergency caesarean section, performed for foetal hypoxia on cardiotocography, and genetic testing of the newborn child using umbilical cord blood was performed at the time of delivery. She will undergo regular screening for uterine, renal and jaw tumours (every 5 years), and is planned for 6-monthly calcium and parathyroid hormone tests. Conclusion Primary hyperparathyroidism is best treated with parathyroidectomy before pregnancy as the maternal and foetal complications increase according to the hypercalcaemia severity. During pregnancy, mild cases could be treated conservatively while parathyroidectomy is reserved for severe cases and is performed in the second trimester. Germline CDC73 analysis is recommended in young pHPT patients, and in this case revealed a pathological variant associated with Hyperparathyroidism-Jaw Tumour syndrome, familial isolated pHPT and parathyroid carcinoma.

Evaluation of the risk of sudden cardiac death in obstructive sleep apnea syndrome patients with Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio

Aims: Obstructive sleep apnea syndrome (OSAS) is a disorder characterized by recurrent collapse of the upper airway during sleep. OSAS is associated with an increased risk of cardiovascular morbidity and mortality. Tpeak to Trend (Tp-e) interval, the Tp-e interval/QT interval (Tp-e/QT) ratio, and the Tp-e interval/corrected QT interval (Tp-e/QTc) ratio, are associated with ventricular arrhythmias and sudden cardiac death in various disease groups. we aimed to investigate the relationship between changes in the new arrhythmia markers Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in OSAS patients. Methods: The study looked at 45 people with OSAS (32 men) over the age of 18 and 43 healthy people (27 men) who were diagnosed with OSAS through polysomnography in a sleep lab. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were calculated on the ECG. Results: The QT interval was shorter in the patient group than in the control group, in contrast to the QTc interval, which was comparable between groups (p = 0.006 and 0.810 in the patient and control groups, respectively). The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were significantly higher in PHPT patients included in the patient group compared to those included in the control group (p&lt;0.01 in total). Conclusion: The Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were prolonged in OSAS patients. These findings suggest that OSAS patients may be predisposed to severe ventricular arrhythmias.

Explorative research on glucolipid metabolism and levels of adipokines in pseudohypoparathyroidism type 1 patients

BackgroundPseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined.ResultsA total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-β index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1.ConclusionMetabolic stress given upon especially overweight PHP1 patients may resulted in possible β-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.

FRI687 Clinical Relevance Of 24-hour Urine Calcium Measurement In Patients With Primary Hyperparathyroidism (PHPT)

Abstract Disclosure: A. Bhan: None. R. Simon: None. G. Jacobsen: None. A. Yaseen: None. P. Navaratnarajah: None. A. Sweidan: None. S.D. Rao: None. Introduction: PHPT is the third most common endocrine disease and the most common cause of hypercalcemia in outpatient setting, presents with mild to moderate hypercalcemia with unsuppressed or elevated serum PTH levels, and most patients are asymptomatic. A 24-hour urine Ca measurement to exclude both hypo- and hypercalciuria is used to recommend parathyroidectomy. The purpose of our study is to evaluate the clinical relevance of urine Ca measurement in evaluating patients with PHPT. Methods: A retrospective electronic medical record review was performed on all adult patients with PHPT in whom a 24-hour urine Ca was measured between 2015-2019. Patients with secondary HPT, those without a 24-hour urine Ca measurement, and patients with serum Cr &amp;gt;1.5 mg/dl were excluded. Results: 393 patients met inclusion criteria for subsequent analyses. For the entire cohort, mean serum Ca was 10.9 ± 0.6 mg/dl, Cr 0.9 ± 0.2 mg/dl and PTH 111± 65 pg/ml with no significant difference between groups by gender, race, or stone history. Mean urine Ca for the entire cohort was 254 ± 170 mg/day. 46% and 35% had urine Ca &amp;gt;250 or &amp;gt;300 mg/d respectively. Multiple linear regression results indicated that higher serum Ca (p=0.004), lower serum Cr (p&amp;lt;0.001), white race (p&amp;lt;0.001), and higher urine sodium (p&amp;lt;0.001) were all significantly predictive of higher UCa. However, the mean urine Ca did not differ between patients with and without nephrolithiasis (276 ± 182 Vs. 280 ± 247 mg/d; p=0.174). Discussion: The most recent guidelines for the management of asymptomatic PHPT recommend measurement of 24-hour urine Ca in all PHPT patients. However, the validity, sensitivity and specificity of such an approach has never been formally evaluated, considering wide variability of urine Ca excretion in the population and lack of difference in urine Ca between patients with and without nephrolithiasis. Previous guidelines discussed this issue and determined that measurement of a 24-hour urine collection is cumbersome and adds very little to patient management. Our study questions the clinical relevance of re-including 24-hour urine Ca in the latest guidelines. Conclusions: Our study suggests that measurement of 24-hour urine Ca in the routine evaluation of patients with PHPT is unhelpful. Presentation: Friday, June 16, 2023

Previous, simultaneous, or subsequent occurrence of malignant tumours in patients with primary hyperparathyroidism: a closer look at the single-tertiary-centre cases.

Our aims were to explore the relationship between primary hyperparathyroidism (pHPT) and malignant tumour development, to determine the frequency and the time of occurrence of malignant tumours in patients with pHPT, and to evaluate the characteristics of pHPT in these patients. This retrospective cohort study included consecutive individuals who were diagnosed with pHPT aged 18 years or older in a university hospital during a 7-year period. A total of 198 patients with pHPT were reviewed retrospectively. Demographic, clinical, biochemical, radiologic findings, and histopathological diagnosis were collected from the electronic medical records of the hospital system. The mean age of the study population was 58 ± 13 years and was predominantly female (female/male: 162/36). There were 42 (21.2%) patients with malignant tumours. Five (12%) out of 42 patients had metachronous double malignancies. The most common 2 concurrent malignancies were breast (36.1%) and thyroid (17.0%). Sixty-eight per cent of the malignant tumours occurred before the diagnosis of pHPT. A higher percentage (87.5%) of simultaneous tumours was seen in the thyroid gland. No statistically significant differences were observed between patients with and without malignant tumours in terms of demographic, clinical, biochemical, radiological, and histopathological features. The median follow-up duration was 24 months after parathyroid surgery. The results of this study revealed that pHPT was associated with various tumour types. The frequency of malignant tumours was 21.2%. Breast and thyroid cancers were the most common 2 cancers coexisting with pHPT. A large percentage of malignant tumours occurred before the diagnosis of pHPT. A higher percentage of simultaneous tumours was seen in the thyroid gland. pHPT patients with and without malignant tumours seemed to have similar characteristics.

Thresholds for surgical referral in primary hyperparathyroidism: A conjoint analysis

BackgroundPrimary hyperparathyroidism (PHPT) can be cured through surgery, but referral for treatment is often provider dependent. A conjoint analysis was performed to identify factors influencing referral for surgery. MethodsOnline survey assessed endocrinologists and other physicians who reviewed 10 patient scenarios. They decided whether to refer for surgery or medical management based on clinical (age, comorbidities, etc) and biochemical factors (mild or classic disease). ResultsClassic PHPT, age below 50, absence of comorbidities, presence of osteoporosis, and seeing a surgical provider significantly increased the likelihood of surgery referral (p < 0.001). Physician characteristics such as gender, practice duration, and setting did not have a significant influence. ConclusionDespite published benefits of surgery, non-surgical physicians were less likely to refer PHPT patients for surgical treatment if patients were older (age ≥ 50), had comorbid conditions, or had mild disease. More education and advocacy are needed for improved access to surgery.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Special features of the diagnostics and treatment of hereditary primary hyperparathyroidism

Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type1 (MEN-1) or show germline mutations of the MEN‑1 gene. Currently, germline mutations that lead to aspecific diagnosis in patients with hpHPT have currently been described in 13different genes, which enables a clear diagnosis of the disease; however, aclear genotype-phenotype correlation does not exist, even though the complete loss of acoded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.

Comparison of Medical Management versus Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism: A Meta-Analysis

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. Results: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p &lt; 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. Conclusions: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.

Does 18F-Fluorocholine PET/CT add value to positive parathyroid scintigraphy in the presurgical assessment of primary hyperparathyroidism?

To investigate the value of presurgical 18F-FCH PET/CT in detecting additional hyperfunctioning parathyroids despite a positive 99mTc-sestamibi parathyroid scintigraphy in patients with primary hyperparathyroidism (pHPT). This is a retrospective study involving patients with pHPT, positive parathyroid scintigraphy performed before 18F-FCH PET/CT, and parathyroid surgery achieved after PET/CT. Imaging procedures were performed according to the EANM practice guidelines. Images were qualitatively interpreted as positive or negative. The number of pathological findings, their topography, and ectopic location were recorded. Histopathology, Miami criterion, and biological follow-up were considered to ensure effective parathyroidectomy confirming the complete excision of all hyperfunctioning glands. The impact of 18F-FCH PET/CT on therapeutic strategy was recorded. 64/632 scanned pHPT patients (10%) were included in the analysis. According to a per lesion-based analysis, sensitivity, specificity, positive predictive value, and negative predictive value of 99mTc-sestamibi scintigraphy were 82, 95, 87, and 93%, respectively. The same values for 18F-FCH PET/CT were 93, 99, 99, and 97%, respectively. 18F-FCH PET/CT showed a significantly higher global accuracy than 99mTc-sestamibi scintigraphy: 98% (CI: 95-99) vs. 91% (CI: 87-94%). Youden Index was 0.79 and 0.92 for 99mTc-sestamibi scintigraphy and 18F-FCH PET/CT, respectively. Scintigraphy and PET/CT were discordant in 13/64 (20%) patients (49 glands). 18F-FCH PET/CT identified nine pathologic parathyroids not detected by 99mTc-sestamibi scintigraphy in 8 patients (12.5%). Moreover, 18F-FCH PET/CT allowed the reconsideration of false-positive scintigraphic diagnosis (scinti+/PET-) for 8 parathyroids in 7 patients (11%). The 18F-FCH PET/CT influenced the surgical strategy in 7 cases (11% of the study population). In a preoperative setting, 18F-FCH PET/CT seems more accurate and useful than 99mTc-sestamibi scan in pHPT patients with positive scintigraphic results. Positive parathyroid scintigraphy could be not satisfactory before neck surgery particularly in patients with multiglandular disease, suggesting a need to evolve the practice and define new preoperative imaging algorithms including 18F-FCH PET/CT at the fore-front in pHPT patients.

Quality of life in patients with primary hyperparathyroidism before and after parathyroidectomy: long term single center experience

BackgroundPrimary hyperparathyroidism (PHPT) is a common endocrine disorder caused by a parathyroid tumor or hyperplasia, which is often accompanied with quality of life (QoL) impairment. A parathyroidectomy (PTX) is the preferred standard treatment for PHPT patients. In this single center study we aimed to evaluate the impact of PHPT on patient’s QoL and identify QoL changes at early and long-term follow-up after surgery.MethodsAll the patients underwent routine PTX with the removal of the suspected hyperparathyroid gland(s). Patients filled out generic QoL questionnaire RAND SF-36, specific questionnaire PHPQoL and specific symptom assessment questionnaire PAS upon admission to the hospital before surgery, at 3 months, 12 months and 24 months after surgery.ResultsA total of 92 patients with PHPT (median age was 56 years, 95.7% females) were included in the study. Before PTX patient’s QoL by SF-36 scores was significantly lower as compared to healthy controls (p < 0.01). Almost 40% of patients had poor or very poor QoL. The most frequent symptoms by PAS before surgery were as follows: tiredness (97.8% of patients), weakness (94.6%), forgetfulness (94.6%), mood changes (90%), feeling “blue”/depression (88%), joint pains (83.3%), headaches (80.2%), constant irritability (77.2%), bone pains (75%), thirst (70.7%) and trouble getting out of a chair (67.4%). The half of the patients had moderate-to-severe (≥ 40 scores) tiredness, weakness, joint pains, forgetfulness, as well as mood changes. Post-operative QoL changes were analysed in the group of 72 patients. After surgery there was significant improvement in QoL by all scales of SF-36 questionnaire, excluding bodily pain, and the PHPQoL total score (GEE, p < 0.01) as compared with their values before surgery. Also severity of tiredness, mood changes, weakness and forgetfulness significantly decreased after surgery as compared to their baseline values (GEE, p < 0.05). Decreased mental component of QoL by PHPQoL (OR = 0.927, 95%CI = 0.874–0.984, p = 0.013) predicted improved QoL after surgery.ConclusionsPatients with PHPT demonstrated significantly impaired QoL in physical, psychological and social functioning as well experienced a wide profile of common PHPT symptoms. Successful PTX was accompanied with remarkable QoL improvement and decrease in subjective symptoms for at least 24 months after surgery.

Update on the current management of persistent and recurrent primary hyperparathyroidism after parathyroidectomy

Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10% of pHPT patients. Preoperative localization imaging is highly valuable. It includes ultrasound, computed tomography (CT), single-photon-emission CT, sestamibi scintigraphy and magnetic resonance imaging. The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months. Ongoing hypercalcemia during this period is defined as persistence, and recurrence is defined as hypercalcemia after six months of normocalcemia. Vitamin D is a crucial factor for a good outcome. Intraoperative parathyroid hormone (PTH) monitoring can safely predict the outcomes and should be suggested. PTH ≤ 40 pg/mL or the traditional decrease ≥ 50% from baseline minimizes the likelihood of persistence. Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology. Risk factors for recurrence are cardiac history, obesity, endoscopic approach and low-volume center (at least 31 cases/year). Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/ recurrence. A 6-mo calcium > 9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up. 18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation. With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement, the recurrence rate has dropped to 2.5%-5%. Six-month serum calcium ≥ 9.8 mg/dL and parathyroid hormone ≥ 80 pg/mL indicate a risk of recurrence. Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels are predictors of multiglandular disease, which brings an increased risk of persistence and recurrence. Bilateral neck exploration was considered the gold-standard diagnostic method. Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques. Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence. Long-term follow-up, even up to 10 years, is necessary.

Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism.

To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients. Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells. No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes. These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.

The Relationship of Negative Imaging Result and Surgical Success Rate in Primary Hyperparathyroidism.

In present, the effect of pre-operative negative imaging results on surgical outcomes of primary hyperparathyroidism (pHPT) is still controversial. In this study, we aimed to evaluate the effect of pre-operative imaging on surgical outcomes. The data of pHPT patients who were operated between 2009 and 2018 were evaluated retrospectively. Patients were divided three groups according to scintigraphy and/or ultrasonography results: Group 1; both imaging positive, Group 2; single imaging positive, and Group 3; patients in whom both imaging modalities are negative. Pre-operative biochemical characteristics, parathyroid pathologies, diameter and volume of the pathological gland, surgery rates, persistence, and recurrent disease rates of the groups were compared. Of 311 patients (258F, 53M) with a mean follow-up period of 24.7±18 months and a mean age of 54.1±12.9 years; 161 were in Group 1, 111 were in Group 2, and 39 were in Group 3. The diameter of pathological gland (2.1±0.8, 1.6±0.9, 1.5±0.7 cm; p<0.001; in Group 1,2,3 respectively) and the volume of pathological gland (2±3.2, 1.4±2.9, 1.1±2.2 cm3; p<0.001; in Group 1,2,3, respectively) in Group 1; the rate of multi gland disease (5.7%, 11%, 21%; p=0.024; in Group 1, 2, 3, respectively) in Group 3 were significantly higher. In the 1, 2, 3 group; bilateral exploration rates were 93.2%, 48.6%, and 5.1%, and focused surgery or unilateral exploration rates were 6.8%, 51.4%, and 94.9%, respectively, with a significant difference (p<0.001). After the first surgery, the cure rate was 91.3%, 93.7%, and 89.7%, and the persistent patient rate was 7.5%, 3.6%, and 10.3% in Groups 1,2,3, respectively, and there was no significant difference. At the end of the follow-up period after secondary intervention applied in persistent and recurrent patients, the overall cure rate was 97.4%, 96.4%, and 97.4%, persistent disease rate 1.3%, 1.8%, and 2.6%, recurrent disease rate 1.3%, 1.8%, and 0%, respectively. In imaging-negative patients with pHPT, the possibility of multi gland disease and smaller pathological glands should be considered at the time of surgery. Surgery in imaging-negative patients can be performed with a similar and acceptable cure rate to imaging-positive patients.